Exploring the Relationship Between YAP (Yes-Associated Protein) and VEGF-A with Distant Metastasis in Nasopharyngeal Carcinoma

Objective: To investigate the relationship between Yes-Associated Protein (YAP) and Vascular Endothelial Growth Factor-A (VEGF-A) in nasopharyngeal carcinoma (NPC) and evaluate their potential as predictive biomarkers for distant metastasis. Methods: This observational analytic study was conducted from May to August 2023, including 60 NPC cases diagnosed histopathologically at the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital. The study involved 30 NPC cases with distant metastasis and 30 without distant metastasis. Immunohistochemical analysis was performed using primary antibodies (rabbit YAP, D8H1X; mouse VEGF, clone C-1 sc-7269). Expression levels of YAP and VEGF-A were semi-quantitatively assessed using the H-score formula on 500 tumor cells. Cutoff points for YAP and VEGF-A were determined through Receiver Operating Characteristic (ROC) curve analysis and the Youden index. Statistical analyses, including Chi-square tests, were conducted using SPSS 25.0 to evaluate the relationship between marker expression and the presence of distant metastasis. Results: A significant difference in YAP expression was observed between NPC cases with distant metastasis (80%) and those without (23.3%, p<0.001). Similarly, VEGF-A expression was notably higher in cases with distant metastasis (86.7%) compared to those without (20%, p<0.001). A significant association between YAP and VEGF-A expression was found (p=0.001). ROC curve analysis showed that YAP (AUC=0.738, 95% CI 0.602-0.874) and VEGF-A (AUC=0.842, 95% CI 0.735-0.950) effectively predict distant metastasis. The double co-high-expression group (elevated YAP and VEGF-A) exhibited a significantly higher rate of distant metastasis compared to the non-double co-high-expression group (p<0.001). Conclusion: Elevated expressions of YAP and VEGF-A are significantly associated with distant metastasis in NPC, suggesting their potential as biomarkers for predicting metastatic risk.